Vasoactive Therapy Research Articles

How important is the measurement of extravascular lung water?

Accurate quantification of extravascular lung water is an important issue in the management of patients with pulmonary edema. The single transpulmonary thermal indicator method has been available since the late 1990s. Its simplicity and easy application make it clinically attractive. Several experimental studies have confirmed the accuracy of the single transpulmonary thermal indicator technique in comparisons with postmortem gravimetric method. Whereas changes in extravascular lung water of less than 100-200% are undetectable by other clinically applicable methods of lung injury assessment (chest radiograph and oxygenation), the single transpulmonary indicator has proven highly sensitive to small (10-20%) increases and is therefore useful to detect incipient pulmonary edema. In patients with sepsis or acute respiratory distress syndrome, extravascular lung water measurement offers information unobtainable by other means. Extravascular lung water can be considered a relevant parameter that contributes to rational management of fluid and vasoactive therapy of many critically ill patients and offers a fuller picture of their overall lung function.

Use of nesiritide before and after publications suggesting drug-related risks in patients with acute decompensated heart failure.

The rate of adoption of new therapies for cardiovascular diseases following the publication of favorable clinical trial results has been studied; however, less is known about the rates of de-adoption of a drug when negative studies are published. To evaluate the use of nesiritide before and after March and April 2005 publications in 2 high-impact journals that suggested an increased risk of renal failure and mortality with intravenous nesiritide for acute decompensated heart failure. Analysis of a large prospective hospital database, developed for quality and utilization benchmarking, of 491 acute care US hospitals at which 385,627 inpatient admissions occurred with a primary International Classification of Diseases, Ninth Revision (ICD-9) code for heart failure between January and August 2001 (prior to nesiritide release) and January 2004 to December 2005 (before and after publication periods). In addition, any patient admitted who received nesiritide in the absence of a primary or secondary heart failure code was evaluated for potential off-label use of the drug. Use of nesiritide and other intravenous vasoactive therapy among patients admitted with heart failure. Nesiritide use decreased from a peak of 16.6% (2351 of 14,167 admissions) in March 2005 to 5.6% (611 of 10,822 admissions) in December 2005 (P<.001). Among those patients treated with nesiritide, the mean duration of treatment changed minimally, from 2.3 to 2.1 days. Although the use of inotropes also decreased during the period under study, the changes were more modest; furthermore, of those patients who were prescribed intravenous vasoactive therapy, a higher percentage were prescribed inotropes after publication (3272 [21.5%] of 15 193 patients from January-April 2005 vs 5750 [29.6%] of 19 445 patients from May-December 2005, P<.001). The use of nesiritide, in the absence of an ICD-9 heart failure code, was small. Rapid de-adoption of nesiritide occurred following 2 publications suggesting risk with the drug. Further analyses are required to evaluate the consequences of these changes on patient outcomes and to anticipate how publications of adverse findings can influence practice.

Vasoactive therapies in systemic sclerosis

In systemic sclerosis (SSc), vasculopathy is a central mechanism and is a major initial event in the process of sclerosis and causing different complications such as Raynaud's phenomenon, ulcer(s) or pulmonary hypertension, the latter being life threatening. Therefore, vasoactive therapies are important when taking care of patients with SSc. However, as treatment has been difficult, numerous therapeutic modalities have been suggested. Until now, the interpretation of most studies is limited due to the heterogeneity of patient groups, the low number of patients, the short duration of the treatments and, possibly, further pathogenic mechanisms such as autoimmunity. Several drugs are now available with effects on vasculopathy and, furthermore, on specific pathogenic mechanisms in SSc. Prostacyclins, endothelin receptor antagonists and phosphodiesterase-5 inhibitors have potential effects on fibrosis, inflammation and endothelial cells, suggesting a disease-modifying capacity in systemic sclerosis. This review summarizes evidence-based therapy recommendations.

The use of self-expanding metal stents to treat acute esophageal variceal bleeding

Acute variceal bleeding is a life-threatening complication of liver cirrhosis. Essential factors for survival after variceal bleeding are the rapidity and efficacy of initial primary hemostasis. Endoscopic and vasoactive therapy is the gold standard in the management of acute variceal hemorrhage. The primary aim of this study was to evaluate the use of self-expandable metallic stents to arrest uncontrollable acute variceal bleeding. Between November 2002 and May 2005, esophageal stents were implanted in 20 patients (18 men, two women; mean age 52, range 27-87) with massive ongoing bleeding from esophageal varices, as an alternative treatment to balloon tamponade. The patients had not been successfully managed with prior pharmacologic or endoscopic therapy. They had had one to five previous bleeding episodes (mean 2.4). Eight of the patients were in Child-Pugh grade B and 12 in grade C. A new type of stent with special introducers was developed that allowed placement without radiographic assistance. The stents were successfully placed in all of the patients and were left in place for 2-14 days. Bleeding from the esophageal varices ceased immediately after implantation of the stent in all cases. While the stent was in place, further diagnostic steps were carried out to optimize management of the patients' illness and portal hypertension. No recurrent bleeding, morbidity, or mortality occurred during treatment with the esophageal stent. All of the stents were extracted without any complications after definitive treatment had been started. In this pilot study, the new method of implantation of an esophageal stent was found to be a safe and effective treatment for massive bleeding from esophageal varices in patients with liver cirrhosis. These initial clinical results will of course have to be confirmed in comparative studies including a large number of patients.

A Cerebrovascular Event After Single-Dose Administration of Recombinant Factor VIIa in a Patient with Esophageal Variceal Bleeding

Upper gastrointestinal bleeding (UGIB) is a life-threatening complication of cirrhosis that develops from esophageal varices in almost 70% of patients. The mortality rate from the bleeding episodes is reported to be 30% [1-4]. Standard management of UGIB of cirrhotic patients is vasoactive therapy combined with endoscopic procedures such as endoscopic sclerotherapy and band ligation [5]. Currently, it is reported that recombinant activated fVIIa (Novoseven, NovoNordisc) can correct the prothrombin time in decompensated cirrhotic patients and also can be used safely in Child's B and C cirrhotic patients with UGIB [6-8]. Herein, we describe the first case report in the literature of a cerebrovascular event after the administration of a single dose of fVIIa in a cirrhotic patient with esophageal variceal bleeding.

Acute Heart Failure Mortality Is Dependent on Time to Intravenous Vasoactive Administration

Background: Vasoactive therapy (nesiritide, nitroglycerin, nitroprusside, dopamine, dobutamine, or milrinone) is used in 28% of acute decompensated heart failure (ADHF) hospitalizations. Our purpose was to determine if clinical outcomes are associated with time to vasoactive initiation after initial presentation in ADHF. Methods: Eligible patients were enrolled in the ADHERE registry and received an IV vasoactive within 48 hours of hospitalization. Excluded were those with a diagnosis of myocardial infarction or troponin I ≥ 1 ng/ml, troponin T ≥ 0.1 ng/ml, troponin positive by qualitative testing, or CKMB% > 5.

Outcomes Associated with Vasoactive Therapy in Patients with Acute Decompensated Heart Failure

To describe the clinical management of acute decompensated heart failure (ADHF) in patients receiving intravenous treatment with dobutamine, milrinone, or nesiritide, and to evaluate differences, based on treatment received, in the in-hospital mortality rate, length of stay (LOS), total health care costs, and 30-day hospital readmission rate. Retrospective cohort analysis. University HealthSystem Consortium (UHC) Clinical Database Pharmacy, a database with information from 32 academic hospitals. Two thousand one hundred thirty patients with ADHF who received dobutamine (1311 patients), milrinone (433), or nesiritide (386). Patients with ADHF were categorized according to the vasoactive therapy received. To evaluate baseline characteristics, chi(2) analysis was used; logistic regression was employed to assess the relationships between drug therapy and in-hospital mortality rates, and multivariate linear regression was used to assess whether drug therapy was related to LOS and total health care costs. All regression analyses controlled for age, sex, race, region of the United States where the hospital was located, primary payer for the hospital stay, UHC patient severity class, and chronic renal failure. In-hospital mortality rates were 10.2%, 7.9%, and 2.9% in the dobutamine, milrinone, and nesiritide groups, respectively. This resulted in an adjusted odds ratio for death of 3.5 (95% confidence interval [CI] 1.8-6.8) for dobutamine and 3.9 (95% CI 1.8-8.3) for milrinone (p<0.0001). Compared with inotropic therapy (dobutamine and milrinone), mean LOS in the hospital and the intensive care unit were lower with nesiritide (p<0.001). Total health care costs were lowest with nesiritide, but this reached statistical significance only when compared with milrinone (p<0.001). Thirty-day hospital readmission rates with dobutamine, milrinone, and nesiritide were 5.0%, 9.5%, and 3.9%, respectively (p=NS). Nesiritide therapy was associated with a lower in-hospital mortality rate and shorter LOS compared with dobutamine and milrinone. In addition, total health care costs with nesiritide were decreased compared with milrinone. These observations need to be validated by a randomized controlled trial.

Gender Differences in In-Hospital Management and Outcomes in Patients With Decompensated Heart Failure: Analysis From the Acute Decompensated Heart Failure National Registry (ADHERE)

Background The impact of gender differences has not been well described in patients hospitalized with acute decompensated heart failure (ADHF). Methods and Results Through review of medical records, data on characteristics, treatments, and outcomes were analyzed on 105,388 patient records according to gender. Women accounted for 52% of these admissions and were older than men (74.5 versus 70.1 years,) and more commonly had preserved left ventricular function (51% versus 28%). Based on history, women were less likely to have coronary artery disease (51% versus 64%) and its risk factors, but more commonly had hypertension (76% versus 70%). Both genders received similar intravenous diuretic regimens, but fewer women received vasoactive therapy (24% vs 31%). Evidence-based oral therapies were underused in both genders. Women consistently received less procedure-oriented therapy. Mean length of stay (women 5.9, men 5.8 days) and the risk-adjusted in-hospital mortality (adjusted odds ratio 0.974 [0.910–1.042], P = .4390) were similar in both genders. Conclusion More women than men are hospitalized with ADHF. Heart failure with preserved left ventricular function predominates in women. Though women are treated less aggressively, treatment gaps exists in both sexes. Despite these differences, length of stay and in-hospital mortality rates are similar.

Impact of anemia on outcome in critically ill patients with severe acute renal failure

To evaluate the prognostic value of hemoglobin levels in critically ill patients with acute renal failure (ARF) requiring dialysis. A prospective observational cohort study in two adult medical ICUs. 206 consecutive patients with ARF who required dialysis. Overall 28-day mortality was 48%. At ICU admission mean hemoglobin level was 9.1+/-2.1 g/dl. By ROC curve analysis the threshold value of hemoglobin with the highest sensibility/specificity was 9 g/dl. At baseline 63% of patients had anemia, defined as initial hemoglobin below 9 g/dl. Kaplan-Meier analysis showed that these patients had lower survival rate than those with hemoglobin above 9 g/dl. By multivariable analysis three factors were independently associated with 28-day death: hemoglobin lower than 9 g/dl (adjusted odds ratio 2.4, 95% CI 1.1-5.2), age, and SOFA score. Based on age and SOFA a matched cohort analysis of 67 pairs of ARF patients with or without anemia found similar results regarding the negative impact of anemia on outcome. Finally, a multivariable logistic regression analysis on matched cohort identified hemoglobin level below 9 g/dl (adjusted odds ratio 1.32, 95%CI 1.15-1.46), continuous renal replacement therapy, and vasoactive therapy as independent predictors of 28-day death. These results suggest that initial hemoglobin level could be helpful in identifying patients with ARF requiring dialysis at high risk of death.

VASOACTIVE THERAPY CAN HELP IMPROVE FUNCTIONAL CAPACITY IN PATIENTS WITH FIBROTIC LUNG DISEASE AND PULMONARY HYPERTENSION

PURPOSE: Interstitial lung disease (ILD) may be associated with hypoxia and pulmonary hypertension (PH). The coexistence of these diseases may produce severe and progressive functional limitation which may be ameliorated by the use of vasoactive therapy. Traditionally vasoactive therapy is not used in such patients due to a perceived lack of benefit and fear of worsening hypoxia.

The Benefits of Early Vasoactive Therapy in the Treatment of Acute Decompensated Heart Failure

To review current issues in the management of acute decompensated heart failure (ADHF), focusing on the early initiation of intravenous (i.v.) vasoactive therapy and including the effects of vasoactive drugs on patient outcomes and the benefits and limitations of each medication class. Review of the worldwide scientific literature on ADHF. The management of ADHF may be improved by early initiation of i.v. vasoactive therapy, reduced use of inotropic agents, and judicious use of diuretics. Data to date suggest that early treatment with the natriuretic peptide nesiritide reduces duration of hospitalization, in-hospital mortality, and requirements for i.v. inotropes and diuretics. Advance practice nurses play an integral role in the management of patients with ADHF from initial triage in the emergency department through final discharge from the hospital. Because they are typically responsible for administering medications and monitoring patient status, nurses need to be familiar with the benefits and limitations of each class of vasoactive agent. They need to recognize that prompt initiation of i.v. vasodilator therapy is important for improving patient outcomes. Further, advance practice nurses should participate in team management that promotes the use of evidence-based ADHF care by developing, using, and assertively communicating the need for processes of care that facilitate best practices.

Neseritide Versus Nitroglycerin for Congestive Heart Failure: A Randomized Trial

Objective: Heart failure is the leading cause of admission for patients over age sixty-five and the large majority of those patients are admitted through the emergency department (ED). Although ED-initiated vasoactive therapy appears to shorten length of stay (LOS) and perhaps improves outcomes, there are remarkably few data as to which form of vasoactive therapy is preferred. The purpose of this prospective, randomized, open-label clinical trial was to determine if intravenous (I.V.) neseritide (NES) was more effective than I.V. nitroglycerin (NTG) in the treatment of acute decompensated heart failure (ADHF) when initiated in the ED.

Strategies to reduce length of stay and costs associated with decompensated heart failure

Heart failure (HF) is a major medical problem in the United States, imposing significant economic burden on the health care system. Despite therapeutic advances, HF-associated morbidity and mortality continue to increase. Compliance with therapeutic guidelines for the management of chronic HF is far from ideal, increasing the likelihood that patients will experience multiple episodes of acute decompensated heart failure (ADHF) during the course of HF disease. Prevention, streamlined inpatient care, effective vasoactive therapy, and initiation of proven long-term therapies, including angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, are all targets for improvement. Because of the chronic nature of heart failure, a successful disease management program for ADHF must also include effective outpatient care.

Principles of Pulmonary Artery Catheterization in the Critically Ill

The pulmonary artery catheter (PAC) may be helpful in determining the etiology of shock, lactic acidosis, pulmonary edema, oliguric renal failure, pulmonary hypertension, and a number of cardiac abnormalities. In addition, it may also be useful in guiding fluid and vasoactive therapy. However, although hemodynamic data from the pulmonary artery catheter (PAC) is widely used diagnostically and therapeutically in the care of critically ill patients, the use of the catheter has not been shown to provide outcomes benefit. In fact, there is some evidence to suggest that placement of the PAC may actually be detrimental. The reasons for this are unclear, but it has been shown that both physicians and nurses frequently misinterpret waveforms and other data obtained from the PAC. Presently, there are a number of ongoing randomized, controlled trials investigating the use of the PAC in specific clinical situations and/or patient populations as well as using specific treatment strategies. In the meantime, if any benefit is to be achieved, it is imperative that clinicians have a thorough understanding of the indications, contraindications, complications, and pitfalls of data interpretation prior to using the catheter. These are reviewed in this article.

Evolving Consensus in Portal Hypertension Report of the Baveno IV Consensus Workshop on methodology of diagnosis and therapy in portal hypertension

Portal hypertension is associated with the most severe complications of cirrhosis, including ascites, hepatic encephalopathy, and bleeding from gastro-esophageal varices. Despite the progress achieved over the last decades, the 6-week mortality associated with variceal bleeding is still in the order of 10–20%. Awareness of the difficulty inherent to the evaluation of diagnostic tools and the design and conduct of good clinical trials for the treatment of portalhypertensionhas led to theorganization, since1986,of a series of consensus meetings. The first one was organized by Andrew Burroughs in Groningen, The Netherlands [1]. After Groningen, other meetings followed, in Baveno in 1990 (Baveno I) [2] and in 1995 (Baveno II) [3,4], in Milan in 1992 [5], in Reston, USA, in 1996 [6], in Stresa in 2000 (Baveno III) [7,8], again in Baveno in 2005 (Baveno IV) [9,10], and in Atlanta in 2007 [11]. The aims of these meetings were to develop definitions of key events in portal hypertension and variceal bleeding, to review the existing evidence on the natural history, the diagnosis and the therapeutic modalities of portal hypertension, and to issue evidence-based recommendations for the conduct of clinical trials and the management of patients. All these meetings were successful and produced consensus statements on some important points, although some issues remained unsettled. To continue the work of the previous meetings, a Baveno V workshop was held on May 21–22, 2010. The workshop was attended by many of the experts responsible for most of the major achievements of the last years in this field. Many of them had attended the previous meetings as well. The main fields of discussion of the Baveno V workshop were the same as in Baveno I–IV, i.e. the definitions of key events concerning the bleeding episode and the therapeutic options in patients with portal hypertension. For each of these topics, a series of consensus statements were discussed and agreed upon. As in Baveno IV, whenever applicable, the level of existing evidence was evaluated and the recommendations were ranked according to the Oxford System [12] (i.e.: level of evidence from 1 = highest

Prognostic Impact of Diabetes Mellitus in Patients With Acute Decompensated Heart Failure

The presence of diabetes mellitus (DM) adversely affects the natural history of heart failure (HF), but its prognostic significance is unknown in acute decompensated HF. Of the 498 patients enrolled with decompensated HF requiring intravenous vasoactive therapy, 236 (47.4%) had a previous diagnosis of DM. After 6 months, 113 patients (22.7%) had died. A Cox proportional-hazards model showed a significant association between DM and worse survival after hospital discharge. DM is common among patients admitted with decompensated HF, and diabetes-related biologic differences contribute to the progression of HF.

MELD score and hepatocellular carcinoma identify patients at different risk of short-term mortality among cirrhotics bleeding from esophageal varices

The role of model for end stage liver disease (MELD) and the presence of hepatocellular carcinoma (HCC) as risk factors of short-term mortality in patients bleeding from oesophageal varices were evaluated. From February 2002 to August 2003, 172 cirrhotic patients admitted for the first episode of bleeding from oesophageal varices received vasoactive and endoscopic therapy. Patients' survival was evaluated at 6 weeks and 3 months. The role of MELD and HCC as independent risk factors of mortality was evaluated. In the 172 patients, the overall mortality was 21.5% at 6 weeks and 30.2% at 3 months. MELD score resulted a good predictor of mortality either at 6 weeks or 3 months. Fifty-four patients (31.3%) had HCC. The presence of advanced HCC was an independent risk factor of mortality at 3 months. Patients with MELD score>15 and advanced HCC had a significantly worse survival than patients with MELD<or=15 and without HCC or with early HCC either at 6 weeks or 3 months MELD score and the presence of HCC allow to identify patients at different risk of short-term mortality among cirrhotic patients at first episode of bleeding from oesophageal varices.

Steroid and Vasoactive Treatment for Acute Deafness after Attempted Hearing Preservation Acoustic Neuroma Surgery

Objective: To investigate whether intravenous steroid and vasoactive therapy in the acute postoperative period improves hearing outcome in patients who develop acute deafness after attempted hearing preservation surgery for acoustic neuroma (AN) through a retrosigmoid or a middle cranial fossa approach. Study Design and Setting: Retrospective controlled study in a tertiary care center. Thirty-six patients who had developed acute deafness after hearing preservation surgery for treatment of an AN were reviewed. Preoperative AAOHNS hearing class was A in 2, B in 2 and D in 32 patients. Twenty-seven patients were treated with prednisolone, hydroxyethyl starch 3% and pentoxifylline intravenously for a period of at least 5 days. Nine patients (controls) did not receive any specific steroid or vasoactive therapy. Results: All patients in both groups remained deaf. Conclusions: Intravenous therapy with prednisolone, hydroxyethyl starch 3% and pentoxifylline in the acute postoperative period does not improve hearing in patients who develop acute deafness after attempted hearing preservation surgery for AN.

ORIGINAL RESEARCH—SURGERY: A Surgical Algorithm for Men with Combined Peyronie's Disease and Erectile Dysfunction: Functional and Satisfaction Outcomes

Men with Peyronie's disease who also have erectile dysfunction represent a challenge to the urologist. Historically, penile prosthesis surgery has been the management strategy of choice for this population. This study was undertaken to define the outcomes of a penile reconstructive surgery algorithm in men with Peyronie's disease and concomitant erectile dysfunction (ED). Patients presenting with combined Peyronie's disease and erectile dysfunction were treated with vasoactive therapy initially. All patients underwent dynamic infusion cavernosometry and cavernosography. Nonresponders to erectogenic pharmacotherapy were advised to undergo penile prosthetic surgery. Responders to erectogenic therapy were considered candidates for either corporoplasty or plaque incision and grafting. The International Index of Erectile Function (IIEF) questionnaire was used to compare erectile function and satisfaction profiles serially pre- and postoperatively between the patients in the three groups. Sixty-two patients constituted the study population. Eighty-one percent of the patients responded to erectogenic pharmacotherapy. Postoperative IIEF erectile function domain scores were statistically higher for implant patients and lower for plaque incision and grafting patients compared to preoperative scores. Postoperative IIEF satisfaction domain scores were higher for corporoplasty and implant patients and lower for plaque incision and grafting patients compared to preoperative scores. The surgical algorithm used in this study leads to excellent IIEF erectile function and satisfaction scores for corporoplasty and implant patients; however, plaque incision and grafting patients had poor functional and satisfaction outcomes. These data support the concept that not all men with combined ED and Peyronie's disease require penile prosthetic surgery, and furthermore, plaque incision and grafting surgery is a poor option for men with combined disease.

From Aspiration to Achievement: Assessment and Noninvasive Treatment of Erectile Dysfunction in Aging Men

More than 70% of elderly men (>or=65) remain sexually active, and more than 40%, according to one estimate, are dissatisfied with their sex lives. Declining sexual function and a reluctance to seek medical attention with advancing age are cross-cultural observations. Normal erection is largely dependent on intact function of the central and peripheral nervous systems and the penile vascular endothelium. Consequently, chronic conditions (e.g., cardiovascular disease, diabetes mellitus) and lifestyle factors (e.g., smoking) that have adverse effects on the vascular endothelium and central and peripheral nervous systems, as well as on endocrine function or connective tissues within the corpus cavernosum of the penis, can attenuate erectile function. Because of these associations, assessment of sexual function in elderly men often reveals not only erectile dysfunction (ED) but also other reversible conditions. An expanding array of noninvasive options is available to assist the clinician in individualizing ED therapy to the unique health and lifestyle needs of each elderly ED patient and his partner. These treatment alternatives include the phosphodiesterase type 5 inhibitors sildenafil, vardenafil, and tadalafil, as well as other oral medications, such as alpha-adrenoceptor antagonists and topical vasoactive or testosterone therapy.